Chapter 2 - Clinical Profile of LAAM
LAAM (levo-alpha-acetyl-methadol) is a synthetic opioid agonist that has recently been approved by the Food and Drug Administration (FDA) for the maintenance treatment of opiate addiction (Food and Drug Administration, 1993). It is not approved for opiate detoxification treatment for either short- or long-term detoxification.
Although LAAM is similar to methadone in many ways, it has several features that make it distinct from methadone. The most significant of these features is LAAM's longer duration of action, which allows patients to visit the treatment program less frequently from treatment inception. The approval of LAAM provides a new treatment alternative in the management of opiate addiction. As such, it should be evaluated by the same standards by which other treatment options have been judged. A new medication should, for example, expand accessibility to treatment, and it should enable more effective and appropriate treatment for patients already in the treatment system. LAAM therapy offers patients such possibilities and creates opportunities for staff members to learn about and provide a new form of care.
In approving LAAM, FDA did not significantly modify the language of the regulations governing methadone treatment. The word "methadone," for example, was simply changed to "narcotic drugs" to be more inclusive. However, differences between the two agents with respect to dosing schedules, prohibition of LAAM take-home doses, and eligibility for LAAM treatment are spelled out in detail in the FDA regulations. As the States begin to approve LAAM and develop their own regulations, many may wish to follow the Federal example. Introduction of LAAM does not require States to develop extensive new regulations. (See Chapter 6 for a discussion of regulations and their development.)
This chapter describes the medication LAAM, including its metabolization, interactions with drugs of abuse and other medications, safety and side effects, and use with certain patient groups, such as women.
Any new medication should expand accessibility to treatment and enable more effective and appropriate treatment for patients already in the treatment system.
Metabolism and Mechanism of Action
The clinical utility of LAAM is based primarily on the activity of two metabolites, rather than on that of the parent drug alone. In the body, LAAM, metabolized by the liver, changes sequentially to nor-LAAM and dinor-LAAM. (Throughout this document, the term LAAM refers to the parent compound and its two active metabolites, nor-LAAM and dinor-LAAM.) Of these three compounds, nor-LAAM is the most potent. The combined duration of activity of all three of these compounds accounts for LAAM's long-acting properties. Knowledge of the basics of steady-state pharmacology is important for understanding the action of LAAM in the body. Steady-state pharmacology is described in Chapter 3 in the section "Induction Onto LAAM."
In practical terms, LAAM's longer action makes it possible for patients to visit the clinic less often than they would for daily methadone treatment. LAAM can be given either every other day or three times a week. Under current FDA regulations, LAAM cannot be given more frequently than every other day, 21 C.F.R. Part 291 Section 291.505(k)(1)(i) (1993), and no take-home doses can be given under any circumstances, 21 C.F.R. Part 291 Section 291.505 (k)(1)(iii) (1993).
Federal regulations also require clinics that use both LAAM and methadone to ensure that "dosage forms of LAAM and methadone are easily distinguished," 21 C.F.R. Part 291 Section 291.505 (1993). LAAM must be different in color and taste from methadone. Methadone is currently available in powder, tablet, and liquid forms, whereas LAAM is currently prepared only in liquid formulation for oral use. The manufacturer provides LAAM as a colorless liquid.
Clinic staff should ensure that patients who are known to abuse sedatives, tranquilizers, propoxyphene, antidepressants, benzodiazepines, or alcohol are told in very clear language of the dangers of adverse additive effects if they take these substances while maintained on LAAM.
At present, LAAM is available only from Roxane Laboratories, Inc. Methadone can be purchased from three different companies: Mallinckrodt Chemical, Inc.; Roxane Laboratories, Inc.; and UDL Laboratories, Inc. Each company markets different forms of methadone that vary in color and taste from the others.
Drug Interactions
Drugs of Abuse
LAAM's interactions with drugs of abuse have not been systematically studied in human populations, but data from the clinical studies do not suggest any unusual risk of LAAM versus other opiates in terms of drug-drug interactions with drugs of abuse. The effects of LAAM would be expected to be similar to the effects of methadone and other opioid drugs under the same conditions. However, until conclusive data from systematic studies are available, interactions cannot be predicted with certainty.
LAAM, like methadone and other opioids, may have additive or synergistic effects when used in combination with commonly used drugs of abuse. Because of LAAM's long-acting nature, both patients and clinic staff should be aware that special caution is necessary when it is combined with drugs that depress the central nervous system, including alcohol. For this reason, clinic staff should ensure that all patients who are known to abuse sedatives, tranquilizers, propoxyphene, antidepressants, benzodiazepines, or alcohol are told in very clear language of the dangers of adverse additive effects if they take these substances while being stabilized or maintained on LAAM.
Experience during the Labelling Assessment Study (LAS) of LAAM indicated that LAAM's delayed onset of effect (from 24 to 36 hours) may lead some patients to take benzodiazepines or other drugs including opiates in an attempt to create an additive effect. Patients receiving LAAM should be counseled very specifically about its delayed onset and prolonged duration of activity, as well as the associated extra risk of effects that can induce withdrawal if patients take other drugs, even on days when they do not receive a LAAM dose. Some patients may not be candidates for LAAM if they are unable to tolerate the slow onset.
Patients receiving LAAM should also be cautioned not to use or abuse alcoholic beverages. Patients should be advised that chronic use of alcohol damages the liver and that liver dysfunction may interfere with the metabolism of LAAM. If alcohol abuse is evident, the program should ensure that the patient receives counseling and assistance in discontinuing alcohol use. If a patient abuses alcohol consistently, a switch to methadone may be warranted because daily clinic attendance will permit closer monitoring, and research has indicated that methadone may be safely prescribed for patients with severe liver damage. Although similar research on LAAM has not been completed, there is every reason to believe that use of LAAM by patients with severe liver damage is not problematic. LAAM may be used concurrently with disulfiram (Antabuse).
Medications That Can Induce Withdrawal
Mixed agonists and antagonists, such as pentazocine (Talwin), butorphanol (Stadol), nalbuphine (Nubain), and buprenorphine (Buprenex), and pure antagonists, such as naltrexone and naloxone, all may precipitate withdrawal in LAAM-maintained patients. FDA has recently approved the narcotic agonist naltrexone for use in treating alcohol craving. Clinicians must be aware and must inform patients that the use of naltrexone will precipitate withdrawal symptoms in patients maintained on LAAM or methadone. Naltrexone must not be used by patients in opioid substitution therapy.
